Author: Marie Powers Source: BioWorld Today (
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Although the concept of cell programming isn't new, Immusoft Corp.'s approach represents a new spin on the science.
For a biotech company, Seattle-based Immusoft started with a decidedly different pedigree. With a background in computer sciences rather than chemistry or biology, Matthew Scholz, the company's founder and CEO, conceived an idea to fight disease by modifying information in human immune cells.
The vision of the computer security expert was to program those cells in much the same way he would program a computer, using technology to turn a patient's B cells into miniature factories for biologic-based therapies addressing a wide range of conditions, including cardiovascular disease, cancers, infectious diseases and lysosomal storage diseases (LSD).
"Instead of letting the body try to randomly patch up the right combination to grab onto whatever it's attacking, we could leverage computational power to develop that novel protein or antibody in a computer and then simply tell the body how to make it," Scholz explained.
As he made the transition from computer science to biotech, "I realized nobody had a suitable technology to program cells that way," Scholz told BioWorld Today. "It seemed so obvious to me that the body is driven by information. Why didn't people figure out how to manipulate that information?"
The quest for that answer led Scholz to the lab of Nobel Prize laureate David Baltimore at the California Institute of Technology, where researchers were using gene transfer methods to reprogram the immune system.
"[Baltimore] was trying to show that you could genetically predispose someone to secrete a particular antibody," Scholz said -- in this case, antibodies against HIV.
In 2009, Scholz licensed exclusive rights to the technology, which is based on an in vitro human B lymphopoiesis culture system, and founded Immusoft.
The Caltech discovery forms the foundation of Immusoft's immune system programming (ISP) platform. Using a novel lentiviral pseudotype discovered in Germany and developed in France, Scholz modified and patented the system, improving its efficiency nearly sevenfold.
The goal of ISP technology is to produce long-lived, biologic-producing plasma cells from a patient's resting B cells. The approach involves harvesting B cells from a simple blood draw, then genetically modifying and differentiating them into plasma cells in vitro. The plasma cells, which have naturally robust protein production capabilities, then are injected back into the patient where they home to the bone marrow, take up survival niches and produce the intended therapeutic.
A suicide gene system is added to the programmed cells to allow for rapid elimination if the therapy is no longer needed.
The company completed proof-of-concept studies in HIV, in collaboration with Seattle Biomedical Research Institute, in which B cells were isolated from the blood of a healthy human donor and successfully modified to produce antibodies against HIV.
Although HIV represents a good fit for the ISP model, "our treatment is very novel and, as such, will probably be viewed with skepticism by the FDA," Scholz acknowledged. "In rare orphan diseases, the regulatory bar is far lower."
Thus, Immusoft's first target, mucopolysaccharidoses Type I (MPS I), is an LSD caused by a defect in the gene coding for a-L-iduronidase (IDUA), affecting a patient's ability to produce IDUA and hindering a process essential for normal tissue growth and maintenance. The rare disease is incurable and usually fatal by age 12.
Immusoft's initial objective is to demonstrate the human immune system can make cells secrete the enzyme needed to treat MPS I and that those modified cells will engraft and function properly in mice.
Although Scholz declined to specify the amount of funding raised by Immusoft, the company received $350,000 in May from the Thiel Foundation's Breakout Labs and $300,000 last month from the National Institutes of Health to test, in collaboration with the Fred Hutchinson Cancer Research Center, whether its ISP platform can program human cells to produce the HIV antibody VRC01 in a mouse model.
Immusoft also has angel funding -- in short, sufficient capital to complete current studies, according to Scholz.
"We're always looking for additional money, and we'll go after VCs at some point," he said, "but our runway is pretty reasonable. The farther we go and the more data we generate, the better our valuation will be."
The company expects to move into primates in one year and to enter human trials in MPS I in three years.
Focusing on MPS I as its first target also will allow the company to demonstrate the technical value of ISP, because the system could induce a patient's bone marrow to produce the required therapy 24/7 at a fraction of the cost of less effective compounds, Scholz said.
He estimated that programming a patient's cells to manufacture his or her own treatments could reduce the cost of MPS I therapy from more than $250,000 a year to less than $500 -- perhaps putting the treatment within reach even in developing nations.
Immusoft remains small -- three full-time and three part-time employees -- but if the company can prove its theory, the sky could be the limit.
"We'd like to partner out the orphan indications," Scholz said, characterizing the diseases as "a stack of dominoes that we can pick off in rapid succession."
Ideally, the company then would seek to apply ISP in heart disease. However, if the technology succeeds in MPS I, "the odds are we would be acquired by the time we ever got to Phase II" in a large indication, Scholz predicted.